The researchers identified a chain of pathogen-favoring events that occurs in the gut lining following antibiotic treatment.
Led by senior author Andreas Bäumler, professor of medical immunology and microbiology, researchers from the University of California-Davis report their discovery in the journal Cell Host & Microbe.
From tests on mice, the team identified a chain of pathogen-favoring events that occurs in the gut lining following treatment with the antibiotic streptomycin.
There is no doubt that since we started using them in the 1940s, antibiotics have saved countless lives. But the rise of antibiotic resistance, and closer examination of their side effects, is causing a rethink in how we use the drugs.
The new finding increases our understanding of how the "good" bacteria in the gut help to protect against "bad" bacteria like Salmonella, and how antibiotics can disturb this relationship by creating conditions that favor disease-causing microbes.
An accompanying editorial says the discovery offers important information that should help develop safer ways to use antibiotics and prevent their side effects.
'Antibiotics enable pathogens in the gut to breathe'
The chain of events that streptomycin triggers begins with reducing populations of "good" gut microbes. These include Clostridia that break down fiber in plant-based foods to make an organic acid called butyrate.
- Antibiotics have been used for the last 70 years to treat infectious diseases
- Each year, over 2 million Americans become infected with antibiotic-resistant bacteria
- At least 23,000 people die in the U.S. each year as a direct result of these infections.
Butyrate is an important resource for cells that line the gut because they use it as an energy source to absorb water.
In the absence of butyrate, the gut-lining cells obtain energy by fermenting glucose to lactate, which is accompanied by an increase in oxygen, a condition that favors the growth of Salmonella. The researchers note:
"We conclude that Salmonella virulence factors and antibiotic treatment promote pathogen expansion through the same mechanism: depletion of butyrate-producing Clostridia to elevate epithelial oxygenation, allowing aerobic Salmonella growth."
Clostridia and other good microbes in the gut grow anaerobically - in the absence of oxygen - whereas Salmonella needs oxygen, so by making the environment oxygen-rich, the antibiotic treatment created conditions favoring the pathogen, explains Prof. Bäumler.
"In essence, antibiotics enabled pathogens in the gut to breathe."
Prof. Andreas Bäumler
The researchers note that previous studies have already shown links between low levels of butyrate-producing microbes and inflammatory bowel disease.
They say further research is now needed to show if what they found is limited to the link between low butyrate and growth of Salmonella, or whether the chain of events also affects other similar mechanisms that could be harmful to health.